The mission of the AIDS Clinical Trials Group (ACTG) is to develop and conduct scientifically rigorous translational research and therapeutic clinical trials to: 1) investigate the viral and immune pathogenesis of HIV-1 infection and its complications;2) evaluate novel therapeutic agents and the most effective approaches and strategies for the use of existing agents to treat HIV-1 infection;3) evaluate interventions and strategies to treat and prevent HIV-related opportunistic infections, co-infections, complications of therapies, and other HIV-1-related co-morbidities, and 4) publish and disseminate the findings from these studies for the purpose of improving clinical care, preventing or delaying HIV disease progression, and reducing or eliminating the morbidity and mortality associated with HIV-1 infection and its associated complications. In this application the ACTG proposes a comprehensive, integrated clinical and translational research program that addresses five of the six scientific areas outlined under this RFA: 1) Translational Research and Drug Development;2) Optimization of Clinical Management, including Co-Infection;3) Vaccine Research and Development;4) Prevention of Mother to Child Transmission, and 5) Prevention of HIV Infection. An Oral Health program will be undertaken in collaboration with investigators supported by the National Institute of Dental and Craniofacial Research. This program will be conducted in collaboration with the HIV Prevention Trials Network (HPTN), the HIV Vaccine Trials Network (HPTN), the IMPAACT network and the Microbicide Trials Network (MTN). The proposed research agenda as well as the Group Leadership and organizational structure reflect the worldwide impact of the HIV epidemic. We propose to conduct the work using a network of 72 clinical research sites in the United States and 12 countries in Africa, Asia, Latin America and the Caribbean. The network is actively supported by an integrated network of Core Laboratories with broad expertise in virology, pharmacology, immunology, and genomics. The ACTG Operations Center, located in Silver Spring, MD, provides key operational, administrative, and fiscal support. Statistical expertise and data management resources are provided by the Statistics and Data Management Center in Boston, MA and Buffalo, NY. CORE (P.I. Benson, Constance) CORE: Translational Research/Drug Development